MKLN1 (muskelin 1) is a component of the CTLH E3 ubiquitin-protein ligase complex with multiple cellular functions. As part of the CTLH complex, MKLN1 mediates ubiquitin-dependent proteasomal degradation of specific substrates. It directly binds FAM72A to target uracil-DNA glycosylase 2 (UNG2) for degradation, promoting mutagenic DNA repair in both immune cells and cancer 12. Additionally, MKLN1 and its binding partner ZMYND19 localize to lysosomal outer membranes to negatively regulate mTORC1 by blocking interactions between mTORC1 and its activator Rheb and substrates S6 and 4E-BP1, enabling rapid tuning of mTOR signaling 3. Beyond ubiquitin-ligase functions, MKLN1 mediates cell spreading and cytoskeletal responses to extracellular matrix components. Genome-wide association studies identified MKLN1 as a colorectal cancer susceptibility gene, with variants associated with reduced cancer risk 4. Its antisense RNA, MKLN1-AS, acts as an oncogenic lncRNA in hepatocellular carcinoma, where it is transcriptionally regulated by SOX9 and stabilizes YAP1 mRNA to promote proliferation and epithelial-mesenchymal transition 56. Circular MKLN1 transcripts demonstrate tumor-suppressive roles in retinoblastoma 7, highlighting context-dependent biological significance across cancer types.